Detecting mitochondrial mutations associated with aminoglycoside ototoxicity by noninvasive prenatal testing

OBJECTIVES: Numerous diseases and disorders are associated with mitochondrial DNA (mtDNA) mutations, among which m.1555A > G and m.1494C > T mutations in the 12 S ribosomal RNA gene contribute to aminoglycoside‐induced and nonsyndromic hearing loss worldwide. METHODS: A total of 76,842 qualified non‐invasive prenatal (NIPT) samples were subjected to mtDNA mutation and haplogroup analysis. RESULTS: We detected 181 m.1555A > G and m.1494C > T mutations, 151 of which were subsequently sequenced for full‐length mitochondrial genome verification. The positive predictive values for the m.1555A > G and m.1494C > T mutations were 90.78% and 90.00%, respectively, a performance comparable to that attained with newborn hearing screening. Furthermore, mitochondrial haplogroup analysis revealed that the 12 S rRNA 1555A > G mutation was enriched in sub‐haplotype D5[p = 0, OR = 4.6706(2.81–7.78)]. CONCLUSIONS: Our findings indicate that the non‐invasive prenatal testing of cell‐free DNA obtained from maternal plasma can successfully detect m.1555A > G and m.1494C > T mutations.